1. Field of the Invention
This invention generally relates to a method for safely stopping the normal heartbeat in order to perform cardiac, aortic, neurovascular and cardiopulmonary organ transplant surgery and other related operations. More particularly, the invention provides a simplified myocardial protection strategy wherein the heart is stopped using adenosine triphosphate (ATP) dependent channel opening agents to shorten the cardiac action potential and hyperpolarize the heart cells. The heart is maintained in a state of minimal metabolic requirement to preserve transmembrane ionic gradients, intercellular energy stores, and cellular integrity during the course of the operation.
2. Description of the Prior Art
Cardiac surgery requires a still and bloodless operative field, therefore necessitating an interruption in the normal blood flow to the heart. The ensuing oxygen deprivation will damage the heart muscle if preservation measures are not instituted. Presently, cardiac surgery operations are performed using a myocardial protection strategy of membrane potential depolarized arrest with increased concentrations of potassium chloride (KCl). Cardioplegia solutions are specially designed solutions which are used during surgery to arrest the heart beat and to place the heart in a state wherein the muscle is at least partially protected from the damaging effects of ischemia. In present surgical practice, the temperature of the heart is typically lowered from the 37.degree. C. normal body temperature to a temperature between 5.degree. C. and 10.degree. C. while perfusing the heart with a cold cardioplegia solution having elevated levels of potassium. The cold temperatures and the elevated levels of potassium act in combination to stop and protect the heart during surgery and, typically, these same conditions are used when transporting the heart for transplantation purposes.
U.S. Pat. No. 5,139,789 to Baumgarten describes the attributes of several cardioplegia solutions in common use today. The Baumgarten patent points out that having controlled potassium and chloride concentrations in the cardioplegia solution, where the product of the potassium and chloride ions in the cardioplegia solution is approximately equal to that found in blood, is important in the control of heart cell swelling during cardioplegia.
Although the advent of modern techniques of cardioplegia and hypothermia have improved and significantly lengthened the safe operating time for complex myocardial revascularization and repair, there has been a marked increase in the incidence of postoperative cardiac arrhythmias, conduction abnormalities, and myocardial injury. Ventricular hypertrophy and reduced myocardial reserves appear clinically to shorten the "safe" time limits of hypothermic cardioplegia. Depolarization of the cardiac cell by a hyperkalemic cardioplegia solution causes derangements in the normal transmembrane distribution of ions, and, most crucially, causes the elevation of intracellular sodium and calcium ions. Recent work has demonstrated that elevated calcium ions produced by an influx of calcium in exchange for sodium (Na.sup.+ --Ca.sup.2+ exchange), or directly through the calcium "window current", is the underlying pathology in triggered arrhythmias, reperfusion injury and the "calcium paradox". While hypothermia is used as a component of cardioplegia because it slows the deleterious metabolic effects of depolarization, cardiac cooling itself causes myocardial injury through alterations in cellular volume regulatory mechanisms and the ensuing myocardial edema. Myocardial edema reduces ventricular function by lessening compliance. Furthermore, hypothermia increases the operative time because of the need to cool and rewarm the patient while on cardiopulmonary bypass.
European Patent Application 0,351,767 to Grover discloses the use of potassium channel activators to inhibit myocardial cell necrosis and to maintain the functioning of the heart during regional myocardial ischemia and/or reperfusion. Grover reports that potassium channel activators, when administered during the regional coronary occlusion period and the reperfusion period, improve performance of the myocardial segment at risk for infarction during and after myocardial ischemia. In practice, experiments using a model of rat portal vein tissue showed that the potassium channel activators cause partial hyperpolarization of the membrane potential and a subsequent decrease in the probability of opening of the voltage dependent calcium channels such that the rate of spontaneous muscle contractions is slowed. The treatment scheme utilizes periodic administration of the potassium channel activators to slow muscle twitching. Having the muscle twitching at slower rate during ischemia and reperfusion was demonstrated to result in decreased contractile dysfunction after ischemia.